2 OP Makarova
adenocarcinoma during 2000–2012 (n = 36248) in Danish Cancer Registry
wasn’t found association between long-term (≥ 5 years) lithium use and
colorectal cancer risk [2]. Treatment with lithium carbonate is not associated
with increased rates of upper urinary tract tumors [3]. This conclusion is made
on results from a nationwide population-based study. On the other hand,
lithium compounds are regarded as potential agents of target therapy, capable
of slowing tumor growth, by inhibiting the enzyme glycogen synthase kinase
3β (GSK-3β) that possesses anti-carcinogenic effects [4]. The tumor cells are
heterogeneous morphologically, the degree of differentiation and the ability to
proliferate. In addition, there are multidrug resistant tumor cells, which
significantly reduce the efficiency of traditional therapy and increase the risk
of recurrence and mortality of patients. In this regard, explores new
therapeutic approaches that can resolve this problem.
PRECLINICAL DATA ON THE ANTITUMOR EFFECT OF
LITHIUM CARBONATE
Currently being studied antitumor influence of officinal forms and
nanosized particles of lithium carbonate. It is known that nanosized particles
have a high cytotoxicity [5]. Lithium carbonate nanosized particles are
available for cells since they have a highly active surface and high sorption
capacity. In addition, lithium carbonate nanosized particles able by slow
dissolution in the tumor microenvironment to inhibit its growth. Lithium ions
can pass through the cell membrane using a selective voltage-dependent
sodium channel [6].
It has been shown in vitro that lithium carbonate nanosized particles have
an inhibitory effect on proliferation of hepatoma-29 cells in lower
concentrations compared to officinal salt form. The basis of the
antiproliferative effect of lithium salts is the activation of tumor cell apoptosis
and delay in phase G 2 /M (phase to mitosis preparation) cell cycle [7]. It was
previously shown that lithium initiates apoptosis of tumor cells HL
indirectly via the activation of expression p53 (a transcription factor, which is
involved in cell cycle regulation and acts as a suppressor of malignant tumors),
Rb (retinoblastoma protein – tumor suppressor protein), Bax (promoter of
apoptosis) and inhibition of expression Bcl-2 (intracellular protein factor that
inhibits apoptosis) and activation of inflammatory cytokine production IL-2,
IL-10 (IL - interleukins) [8]. Anti-apoptotic signaling is regulated by GSK- 3